tert-Butanol → Methyl 2-((tert-butoxycarbonyl)amino)-3-nitrobenzoate

Participants

Reaction Conditions

Reaction Steps

Methyl 2-carboxy-3-nitrobenzoate [MNA] obtained in Reference Example 2 (164 kg) was dissolved in dimethylformamide [DMF] (242 kg), diphenylphosphoryl azide [DPPA] (204 kg) was added thereto at room temperature, and triethylamine (87 kg) was added dropwise while maintaining at 20 to 35° C. After stirring at 20 to 30° C. for about 3 hours, t-butyl alcohol (930 kg) was added to the reaction solution. The temperature was risen to 85 to 90° C. over 3 to 5 hours, and the solution was stirred for 1 to 2 hours under reflux (85 to 90° C.). The reaction solution was cooled, concentrated, and the residue was dissolved in ethyl acetate (1400 L). The solution was washed successively with a mixture of 15% hydrochloric acid (160 L) and water (1890 L), water (660 L), 5% aqueous sodium bicarbonate solution (1100 kg) and water (660 L), and the organic layer was concentrated under reduced pressure. Methanol (300 kg) was added thereto, and concentrated under reduced pressure. A seed crystal (15 kg) and methanol (450 kg) were added to the residue, and the mixture was heated to 50 to 60° C. to dissolve it. After cooled to 5° C., crystals were separated, washed with cold methanol (100 L), and dried to give methyl 2-t-butoxycarbonylamino-3-nitrobenzoate [BAN] (187.0 kg, 86.7%). The mother liquor and the washing were concentrated under reduced pressure, and cooled. The precipitated crystals were centrifuged, washed with cold methanol, and dried to give second crystal of BAN.

Provenance & Evidence